Atherosclerosis最新文献

{"title":"Association of colchicine use with cardiovascular and limb events in peripheral artery disease: Insights from a retrospective cohort study","authors":"Lucas Tramujas ,&nbsp;Alleh Nogueira ,&nbsp;Nicole Felix ,&nbsp;Pedro Gabriel Melo de Barros e Silva ,&nbsp;Alexandre Abizaid ,&nbsp;Alexandre Biasi Cavalcanti","doi":"10.1016/j.atherosclerosis.2024.118563","DOIUrl":"10.1016/j.atherosclerosis.2024.118563","url":null,"abstract":"<div><h3>Background and aims</h3><div>Colchicine has demonstrated efficacy in treating coronary artery disease, but its efficacy in peripheral artery disease (PAD) remains uncertain. This study aims to address this gap in knowledge.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using the TriNetX Network, selecting patients with lower limb PAD between January 1, 2011, and January 1, 2024. Colchicine users were matched 1:1 with non-users through propensity score matching, considering demographics, medical conditions, medications, and psychosocial factors. The primary outcome was a composite of major adverse cardiovascular and limb events (MACLE) - including lower limb amputation, revascularization for lower limb ischemia, acute myocardial infarction, ischemic stroke, and all-cause mortality – over a ten-year follow-up.</div></div><div><h3>Results</h3><div>From 53,568 colchicine-treated and 1,499,969 untreated patients with lower limb PAD, 52,350 pairs were successfully matched. Over ten years, colchicine was associated with a significant reduction in MACLE (hazard ratio, [HR] 0.90, 95% CI 0.88–0.92<em>, p</em> &lt; 0.001), any lower limb amputation (HR 0.84, 95% CI 0.75–0.94, <em>p</em> = 0.002), revascularization for lower limb ischemia (HR 0.85, 95% CI 0.82–0.88, <em>p</em> &lt; 0.001), major adverse cardiovascular events (HR 0.93, 95% CI 0.91–0.95, <em>p</em> &lt; 0.001), and all-cause mortality (HR 0.90, 95% CI 0.87–0.92, <em>p</em> &lt; 0.001). It also result in a reduced risk of ischemic stroke (HR 0.95, 95% CI 0.92–0.98, <em>p</em> = 0.001), but not of acute myocardial infarction (HR 0.98, 95% CI 0.95–1.01<em>, p</em> = 0.24).</div></div><div><h3>Conclusions</h3><div>Colchicine significantly reduced major adverse cardiovascular and limb events in patients with lower limb PAD, supporting the need for further investigation.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118563"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of fatty acids in the pathogenesis of ß-cell failure and Type-2 diabetes","authors":"Cecilia Jiménez-Sánchez,&nbsp;Lucie Oberhauser,&nbsp;Pierre Maechler","doi":"10.1016/j.atherosclerosis.2024.118623","DOIUrl":"10.1016/j.atherosclerosis.2024.118623","url":null,"abstract":"<div><div>Pancreatic ß-cells are glucose sensors in charge of regulated insulin delivery to the organism, achieving glucose homeostasis and overall energy storage. The latter function promotes obesity when nutrient intake chronically exceeds daily expenditure. In case of ß-cell failure, such weight gain may pave the way for the development of Type-2 diabetes. However, the causal link between excessive body fat mass and potential degradation of ß-cells remains largely unknown and debated. Over the last decades, intensive research has been conducted on the role of lipids in the pathogenesis of ß-cells, also referred to as lipotoxicity. Among various lipid species, the usual suspects are essentially the non-esterified fatty acids (NEFA), in particular the saturated ones such as palmitate. This review describes the fundamentals and the latest advances of research on the role of fatty acids in ß-cells. This includes intracellular pathways and receptor-mediated signaling, both participating in regulated glucose-stimulated insulin secretion as well as being implicated in ß-cell dysfunction. The discussion extends to the contribution of high glucose exposure, or glucotoxicity, to ß-cell defects. Combining glucotoxicity and lipotoxicity results in the synergistic and more deleterious glucolipotoxicity effect. In recent years, alternative roles for intracellular lipids have been uncovered, pointing to a protective function in case of nutrient overload. This requires dynamic storage of NEFA as neutral lipid droplets within the ß-cell, along with active glycerolipid/NEFA cycle allowing subsequent recruitment of lipid species supporting glucose-stimulated insulin secretion. Overall, the latest studies have revealed the two faces of the same coin.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118623"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phospholipid-derived lysophospholipids in (patho)physiology","authors":"Patricia Prabutzki,&nbsp;Jürgen Schiller,&nbsp;Kathrin M. Engel","doi":"10.1016/j.atherosclerosis.2024.118569","DOIUrl":"10.1016/j.atherosclerosis.2024.118569","url":null,"abstract":"<div><div>Phospholipids (PL) are major components of cellular membranes and changes in PL metabolism have been associated with the pathogenesis of numerous diseases. Lysophosphatidylcholine (LPC) in particular, is a comparably abundant component of oxidatively damaged tissues. LPC originates from the cleavage of phosphatidylcholine (PC) by phospholipase A₂ or the reaction of lipids with reactive oxygen species (ROS) such as HOCl. Another explanation of increased LPC concentration is the decreased re-acylation of LPC into PC. While there are also several other lysophospholipids, LPC is the most abundant lysophospholipid in mammals and will therefore be the focus of this review.</div><div>LPC is involved in many physiological processes. It induces the migration of lymphocytes, fostering the production of pro-inflammatory compounds by inducing oxidative stress. LPC also “signals” via G protein-coupled and Toll-like receptors and has been implicated in the development of different diseases. However, LPCs are not purely “bad”: this is reflected by the fact that the concentration and fatty acyl composition of LPC varies under different conditions, in plasma of healthy and diseased individuals, in tissues and different tumors.</div><div>Targeting LPC and lipid metabolism and restoring homeostasis might be a potential therapeutic method for inflammation-related diseases.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118569"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB2 promotes smooth muscle cell proliferation through PPAR-γ/PGC-1α pathway-mediated glucose changes in aortic dissection","authors":"Yameng Zheng ,&nbsp;Mengge Yao ,&nbsp;Shaokun Chen ,&nbsp;Jiakang Li ,&nbsp;Xiaozhen Wei ,&nbsp;Zhihuang Qiu ,&nbsp;Liangwan Chen ,&nbsp;Li Zhang","doi":"10.1016/j.atherosclerosis.2024.119044","DOIUrl":"10.1016/j.atherosclerosis.2024.119044","url":null,"abstract":"<div><h3>Background and aims</h3><div>Aortic dissection (AD) is a fatal condition with a complicated pathogenesis. High mobility group protein B2 (HMGB2) is a member of the high mobility group protein family; HMGB2 is involved in innate immunity and inflammatory diseases, but its role in AD remains unclear.</div></div><div><h3>Methods</h3><div><em>HMGB2</em>^{<em>−/−</em>} mice were generated and treated with β-aminopropionitrile and angiotensin II (Ang II) to establish an AD model. An F12 gel containing AAV9-HMGB2 was applied to overexpress HMGB2 in mice. Pathological changes in the aorta were assessed by visualizing vascular collagen deposition and elastic fiber fracture via H&amp;E, Masson and EVG staining. HMGB2 expression was measured by Western blotting and immunohistochemistry. MTS, CCK-8 and EdU assays were used to test cell proliferation.</div></div><div><h3>Results</h3><div>HMGB2 expression was increased in samples from AD patients, samples from AD mouse modeland human aortic smooth muscle cells (HASMCs). HMGB2 promoted HASMC proliferation. Immunofluorescence staining and plasma membrane protein isolation revealed that HMGB2 decreased GLUT1 expression and promoted GLUT4 translocation. HMGB2 was also found to inhibit the expression of SIRT1/PGC-1α, but blocking the PPAR-γ pathway attenuated this effect. <em>HMGB2</em>^{<em>−/−</em>} significantly reduced the incidence and mortality rates of AD, whereas treatment with AAV9-HMGB2 exacerbated AD.</div></div><div><h3>Conclusions</h3><div>This study suggests that HMGB2 promotes HASMC proliferation and vascular remodeling by regulating glucose metabolism through the PPAR-γ/SIRT1/PGC-1α pathway. HMGB2 knockdown reduces, while HMGB2 overexpression promotes, the occurrence of AD in mice. This study may help elucidate the underlying mechanisms and provide a new preventive target for AD.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 119044"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of maintaining lower LDL-C level during statin treatment for advanced CKD patients","authors":"Chieh-Li Yen ,&nbsp;Pei-Chun Fan ,&nbsp;Cheng-Chia Lee ,&nbsp;Jia-Jin Chen ,&nbsp;Chao-Yu Chen ,&nbsp;Yi-Ran Tu ,&nbsp;Pao-Hsien Chu ,&nbsp;Ching-Chung Hsiao ,&nbsp;Yung-Chang Chen ,&nbsp;Chih-Hsiang Chang","doi":"10.1016/j.atherosclerosis.2024.119042","DOIUrl":"10.1016/j.atherosclerosis.2024.119042","url":null,"abstract":"<div><h3>Background and aims</h3><div>Different from other high cardiovascular (CV) risks populations, the evidence supporting the CV protective effect of LDL-C reduction with statins in chronic kidney disease (CKD) patients is comparatively scarce. This study is aimed to investigate the role of maintaining lower LDL-C level in advanced CKD patients.</div></div><div><h3>Methods</h3><div>By using Chang Gung Research Database, on the basis of Taiwan's largest healthcare group, a total of 5367 adult patients newly-diagnosed with stage 4 CKD and receiving statin were extracted and further categorized into three groups based on their LDL-C levels: &lt;70 mg/dL, 70–100 mg/dL, and ≥100 mg/dL. The main outcome is major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiovascular death, myocardial infarction, and stroke. The inverse probability of treatment weighting was performed to achieve balance of baseline characteristics.</div></div><div><h3>Results</h3><div>At 5-year follow-up, the LDL-C &lt; 70 mg/dL group exhibited significantly lower risks of MACCEs (14.3 % vs. 18.7 %, hazard ratio [HR]: 0.77, 95 % CI: 0.69–0.86), cardiovascular death (7.1 % vs. 9.7 %, subdistribution HR [SHR]: 0.75, 95 % CI: 0.65–0.88), ischemic stroke (4.1 % vs. 5.4 %, [SHR]: 0.65, 95 % CI: 0.54–0.79), and new-onset end-stage renal disease requiring chronic dialysis (25.6 % vs. 29.4 %, SHR: 0.87, 95 % CI: 0.80–0.91) compared to LDL-C &gt; 100 mg/dL group. In contrast, the group with LDL-C levels between 70 and 100 did not significantly differ from the group with LDL-C &gt; 100 mg/dL in study outcomes.</div></div><div><h3>Conclusions</h3><div>Maintaining LDL-C lower than 70 mg/dL may be beneficial for cardiovascular protection in advanced CKD patients and a lower LDL-C treatment target may be required as CKD progression.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 119042"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement factor B, not the membrane attack complex component C9, promotes neointima formation after arterial wire injury","authors":"Ziyi Guo ,&nbsp;Yuze Zhang ,&nbsp;Zekun Peng ,&nbsp;Haojie Rao ,&nbsp;Jianfeng Yang ,&nbsp;Zengrong Chen ,&nbsp;Wenchao Song ,&nbsp;Qing Wan ,&nbsp;Hong Chen ,&nbsp;Miao Wang","doi":"10.1016/j.atherosclerosis.2024.118586","DOIUrl":"10.1016/j.atherosclerosis.2024.118586","url":null,"abstract":"<div><h3>Background and aims</h3><div>Vascular restenosis due to neointima hyperplasia limits the long-term patency of stented arteries, resulting in angioplasty failure. The complement system has been implicated in restenosis. This study aimed to investigate the role of complement factor B (fB), an essential component of the alternative pathway of complement activation, in neointima formation.</div></div><div><h3>Methods</h3><div>Angioplasty wire injury was conducted using 12-week-old mice deficient in fB or C9 (the main component of the membrane attacking complex, C5b-9) and littermate controls and neointima formation were assessed. Vascular smooth muscle cell (SMC) and endothelial cell (EC) proliferation and migration were examined <em>in vitro</em>.</div></div><div><h3>Results</h3><div>fB was mainly detected in SMCs of stenotic arteries from humans and mice. Deletion of fB substantially reduced the neointima area and intima-to-media area ratio without affecting the media area at 28 days after injury. At 7 days after injury, fB deficiency decreased SMC proliferation, unaltering neointimal macrophage infiltration and EC reendothelialization. Vascular SMC-expressed fB, not the circulation-sourced fB, played an essential role in SMC proliferation and migration <em>in vitro</em>. fB deficient mice exhibited lower levels of the soluble form of C5b-9, however, deletion of C9 did not alter neointima formation after wire injury, consistent with the null impact of C9 deficiency on SMC proliferation <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>fB promotes neointima formation following wire-induced artery injury independent of forming the membrane-attacking complex. This is attributable to fB-dependent SMC proliferation and migration without affecting EC function. Targeting fB might protect against restenosis after percutaneous coronary intervention.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118586"},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting LDL aggregation decreases atherosclerotic lipid burden in a humanized mouse model of familial hypercholesterolemia: Crucial role of ApoB100 conformational stabilization.","authors":"A Benitez-Amaro, E Garcia, M T La Chica Lhoëst, A Martínez, C Borràs, M Tondo, M V Céspedes, P Caruana, A Pepe, B Bochicchio, A Cenarro, F Civeira, R Prades, J C Escola-Gil, V Llorente-Cortés","doi":"10.1016/j.atherosclerosis.2024.118630","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118630","url":null,"abstract":"<p><strong>Background and aims: </strong>Low-density lipoprotein (LDL) aggregation is nowadays considered a therapeutic target in atherosclerosis. DP3, the retro-enantio version of the sequence Gly¹¹²⁷-Cys¹¹⁴⁰ of LRP1, efficiently inhibits LDL aggregation and foam cell in vitro formation. Here, we investigate whether DP3 modulates atherosclerosis in a humanized ApoB100, LDL receptor (LDLR) knockout mice (Ldlr^-/-hApoB100 Tg) and determine the potential LDL-related underlying mechanisms.</p><p><strong>Methods: </strong>Tg mice were fed an HFD for 21 days to induce atherosclerosis and then randomized into three groups that received a daily subcutaneous administration (10 mg/kg) of i) vehicle, ii) DP3 peptide, or iii) a non-active peptide (IP321). The in vivo biodistribution of a fluorescent-labeled peptide version (TAMRA-DP3), and its colocalization with ApoB100 in the arterial intima, was analyzed by imaging system (IVIS) and confocal microscopy. Heart aortic roots were used for atherosclerosis detection and quantification. LDL functionality was analyzed by biochemical, biophysical, molecular, and cellular studies.</p><p><strong>Results: </strong>Intimal neutral lipid accumulation in the aortic root was reduced in the DP3-treated group as compared to control groups. ApoB100 in LDLs from the DP3 group exhibited an increased percentage of α-helix secondary structures and decreased immunoreactivity to anti-ApoB100 antibodies. LDL from DP3-treated mice were protected against passive and sphingomyelinase (SMase)-induced aggregation, although they still experienced SMase-induced sphingomyelin phospholysis. In patients with familial hypercholesterolemia (FH), DP3 efficiently inhibited both SMase-induced phospholysis and aggregation.</p><p><strong>Conclusions: </strong>DP3 peptide administration inhibits atherosclerosis by preserving the α-helix secondary structures of ApoB100 in a humanized ApoB100 murine model that mimicks the hallmark of human hypercholesterolemia.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118630"},"PeriodicalIF":4.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins","authors":"Ankia Visser ,&nbsp;Willemien van Zwol ,&nbsp;Niels Kloosterhuis ,&nbsp;Nicolette Huijkman ,&nbsp;Marieke Smit ,&nbsp;Mirjam Koster ,&nbsp;Vincent Bloks ,&nbsp;M. Mahmood Hussain ,&nbsp;Bart van de Sluis ,&nbsp;Jan Albert Kuivenhoven","doi":"10.1016/j.atherosclerosis.2024.118635","DOIUrl":"10.1016/j.atherosclerosis.2024.118635","url":null,"abstract":"<div><h3>Background and aims</h3><div>The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood.</div></div><div><h3>Methods and Results</h3><div>Using human transcriptome datasets to find genes co-regulated with <em>MTTP</em>, we identified <em>ERICH4</em> as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between <em>ERICH4</em> and plasma lipids. To validate <em>ERICH4</em> as a lipid gene, we generated whole-body <em>Erich4</em> knockout (<em>Erich4</em>^{<em>−/−</em>}) mice. ERICH4 deficiency<em>,</em> however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either.</div></div><div><h3>Conclusions</h3><div>Despite prediction tools indicating <em>ERICH4</em> as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118635"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publication bias in pharmacogenetics of statin-associated muscle symptoms: A meta-epidemiological study.","authors":"A Gougeon, I Aribi, S Guernouche, J C Lega, J M Wright, C Verstuyft, A Lajoinie, F Gueyffier, G Grenet","doi":"10.1016/j.atherosclerosis.2024.118624","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.118624","url":null,"abstract":"<p><strong>Background and aims: </strong>Statin-associated muscle symptoms (SAMS) are a major cause of treatment discontinuation. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend dose adjustment for statin treatment according to known SLCO1B1 genotype to reduce SAMS. We hypothesized that the association between SLCO1B1 genotype and SAMS is misestimated because of publication bias.</p><p><strong>Methods: </strong>We searched published systematic reviews on the association between SLCO1B1 genotype and SAMS. To assessed publication bias, we used funnel plot visual inspection, Egger's test, and the Bayes Factor (BF_{Publication-bias}) from Robust Bayesian Meta-Analysis (RoBMA). We compared the odds ratios (OR_Uncorrected) from meta-analyses before and after correcting for publication bias using trim-and-fill (OR_Trim&Fill) and RoBMA (OR_RoBMA) methods.</p><p><strong>Results: </strong>We included 8 cohort and 11 case-control studies, totaling 62 OR of three SLCO1B1 genotypes and six statin drugs. In the primary analysis, the funnel plot was suggestive of publication bias, confirmed by Egger's test (p=0.001) and RoBMA (BF_{Publication-bias} = 18). Correcting the estimate for publication bias resulted in loss of the association, from a significant OR_Uncorrected (1.31 95%CI [1.13-1.53]) to corrected ORs suggesting no difference: OR_Trim&Fill (1.07 95%CI [0.89-1.30]) and OR_RoBMA (1.02 95%CI [1.00-1.33]). This suggested that publication bias overestimated the association by 18 % and 23 %, respectively. Similar results were found for genotype rs4149056, simvastatin and atorvastatin.</p><p><strong>Conclusions: </strong>The effect of the SLCO1B1 genotype on the risk of developing SAMS is overestimated in the published literature, especially rs4149056. This could lead prescribers to incorrectly decreasing statin doses or even avoiding statin use, leading to a loss of the potential cardiovascular benefit of statins.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"118624"},"PeriodicalIF":4.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial","authors":"Daniel Goeder ,&nbsp;Julia Maria Kröpfl ,&nbsp;Thomas Angst ,&nbsp;Henner Hanssen ,&nbsp;Christoph Hauser ,&nbsp;Denis Infanger ,&nbsp;Debbie Maurer ,&nbsp;Renate Oberhoffer-Fritz ,&nbsp;Arno Schmidt-Trucksäss ,&nbsp;Karsten Königstein","doi":"10.1016/j.atherosclerosis.2024.118631","DOIUrl":"10.1016/j.atherosclerosis.2024.118631","url":null,"abstract":"<div><h3>Background and aims</h3><div>Endothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50 % of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs).</div></div><div><h3>Methods</h3><div>Sedentary adults with elevated CV risk between 40 and 60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n = 30) or received standard exercise recommendations (n = 14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses.</div></div><div><h3>Results</h3><div>baFMD improved by 2.38 % (CI:0.70–4.06, <em>p</em> = 0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2 % of dataset variability was higher in the NLPE-group compared to the control group (2.71 ± 2.02 <em>vs.</em> 1.65 ± 0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD.</div></div><div><h3>Conclusions</h3><div>The improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118631"},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}